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Selective P2Y 6 ‐Receptor Antagonism as a Putative Treatment for Detrusor Overactivity
Author(s) -
Ikeda Youko,
Roppolo James,
Fry Christopher,
Wu Changhao,
Kanai Anthony
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.656
Subject(s) - urothelium , receptor , urinary bladder , medicine , blockade , pulmonary stretch receptors , overactive bladder , endocrinology , urology , chemistry , pathology , alternative medicine
Augmentation of intrinsic spontaneous contractions of the urinary bladder in pathology may contribute to bladder overactivity. Spontaneous activity was investigated using Ca 2+ and voltage optical mapping combined with tension recordings of whole bladder sheets from control and spinal cord transected (SCT) rats. SCT preparations showed high amplitude contractions with regular periodicity while normal bladders displayed smaller contractions with a higher frequency. Ca 2+ and voltage isochronal maps from mucosal surfaces showed a single focal ‘pacemaker‐like’ initiation site in the dome of SCT bladders, while controls displayed randomly occurring multiple initiation sites. The amplitude of contractions was increased by stretch (64±21% from control) and 50nM arecaidine (59±17% from control) in SCT but not normal preparations. It is hypothesized that pacemaker‐like activity in SCT animals may be mediated through lamina propria myofibroblasts (LPM) that respond to stretch‐released ATP from the urothelium. Blockade of LPM‐specific P2Y 6 ‐receptors with 10μM MRS2578 decreased contractions in SCT (36±22% from control) but not control bladders. Targeting of LPM P2Y 6 ‐receptors may offer an alternative therapeutic treatment to anticholinergics for bladder overactivity. The research was sponsored by the NIH (DK064280) and awards from Pfizer.